Multiple Infections and Cancer: Implications in Epidemiology

Vedham, Vidya; Divi, Rao L.; Starks, Vaurice L.; Verma, Mukesh

doi:10.7785/tcrt.2012.500366

Cited by 45 publications

(42 citation statements)

References 238 publications

(311 reference statements)

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“…Second, other unknown infection(s) may increase the chance of HPV infection. These multiple infections may affect a woman's susceptibility to HPV, or its persistence (17). Lee et al showed that changes in vaginal microbiota in post-menopausal women made them more susceptible to HPV infection (18).…”

Section: Discussionmentioning

confidence: 99%

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Prevalence and genotype distribution of human papillomavirus among Hakka women in China

Zeng¹,

Yan²,

Huang³

et al. 2016

Ann. Transl. Med.

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Background: Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPV genotypes are associated with varying degrees of pathogenicity. To better formulate strategies for cervical cancer prevention, we investigated the population-specific distribution of HPV genotypes, including those with high carcinogenicity. Results: Risk stratification based on genotypes indicated that the prevalence of overall, high-risk, and low-risk HPV infections was 12.27%, 14.20%, and 0.79%, respectively. Of the 1,003 women positively infected, 82.75%were infected with a single HPV type; 17.25% were infected with ≥2 types. Analysis revealed a U-shaped curve in HPV prevalence that correlated with age group, with peaks at ages 18-24 y (22.03%) and 60-65 y (25%). The most frequently detected HPV genotype was HPV-52 (26.81%), and then HPV-16 (17.54%), HPV-58 (14.25%), HPV-18 (10.16%), HPV-68 (8.27%), HPV-39 (5.68%), and HPV-51 (5.38%).Conclusions: HPV-52 is the most prevalent genotype infecting Hakka women. Therefore, vaccination against HPV-52 is imperative. The prevalence of HPV infection is highest in the younger (18-24 y) and older (60-65 y) age groups, indicating that screening for HPV in Hakka women should be performed early and maintained in the elderly.

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Section: Discussionmentioning

confidence: 99%

“…HPV, human papillomavirus. developing cervical cancer (17). However, the interaction of various genotypes in co-infections remains unclear, and future studies are needed to verify whether coordinated mechanisms in co-infections exist.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and genotype distribution of human papillomavirus among Hakka women in China

Zeng¹,

Yan²,

Huang³

et al. 2016

Ann. Transl. Med.

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“…While the E6 protein of HPV inactivates p53 and E7 inactivates the retinoblastoma (Rb) tumor suppressor protein, detailed studies on a large number of tumors indicate that viral infection alone is not sufficient for tumor development. Studies have also shown that 20 to 30 million Americans are infected with HPV (7). However, only those in a subset develop cervical cancer.…”

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confidence: 99%

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

Soh

Venkatesan

Veena

et al. 2016

Molecular and Cellular Biology

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Cervical cancer is the second-most-common cancer responsible for cancer-related death in women around the world. The incidence is increasing, with 450,000 new cases diagnosed worldwide and 12,340 diagnosed in the United States annually (1, 2). It is the third leading cause of death from cancer in women 15 to 34 years of age and the fifth leading cause of death in women 35 to 54 years of age, representing about 2% of all cancers in women in the United States. The disease is frequently found in women who have had multiple sex partners, smoking habits, and immune system dysfunctions (3). Cervical cancer is closely linked with human papillomavirus (HPV) infection, and HPVs are detected in 90% of cervical cancer lesions (4-6). While the E6 protein of HPV inactivates p53 and E7 inactivates the retinoblastoma (Rb) tumor suppressor protein, detailed studies on a large number of tumors indicate that viral infection alone is not sufficient for tumor development. Studies have also shown that 20 to 30 million Americans are infected with HPV (7). However, only those in a subset develop cervical cancer. Recently, HPVs have been implicated in the development of head and neck, lung, and breast cancers (8-10).Cystatins are inhibitors of cysteine proteases and are classified into a large superfamily subdivided into three families based on their location, size, and complexity of polypeptide chains (11-13). Cystatin E/M belongs to the type 2 cystatin family (cystatin C, D, E/M, F, S, SA, and SN), whose members are mainly secreted, and most of them are found abundantly in body fluids and tissues. Cystatin E/M is present as an unglycosylated 14-kDa form containing 149 amino acids and a 17-kDa form that is glycosylated. Loss of this protein seems to play a significant role in abnormal skin development (14). A null mutation of the mouse cystatin E/M gene is also correlated with development of the ichq phenotype, characterized by neonatal lethality, abnormal cornification, and desquamation. Cystatin E/M was initially identified as a downregulated transcript in metastatic breast cancers (15,16). A number of studies have implicated cystatin E/M as a human tumor suppressor gene that is inactivated in the cancers of the breast, cervix, prostate, brain, and stomach (17-23). Our studies have also shown that the inactivation of the gene is associated with homozygous deletion, promoter hypermethylation, and somatic mutations in primary tumor samples (19). Cystatin E/M gene is expressed in ductal carcinoma in situ (DCIS) but not in metastatic breast cancer, pointing to inactivation during tumor progression (16)(17)(18)24). Finally, inactivation of cystatin E/M gene is associated with the loss of expression of estrogen and progesterone receptors and HER4, indicating an association with these proteins in the development of invasive breast cancers (25). However, the molecular mechanism of cystatin E/M-mediated tumor cell growth inhibition is not yet understood.Cathepsins include a broad range of proteases, the serine (A

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“…To examine the intracellular processing of HPV16 PsV, 4 ϫ 10 5 HaCaT cells/well were plated in 6-well plates overnight and then treated with 2 ng/ml IFN-␥ prior to incubation with PsV. Nine hundred nanograms of PsV, based on L1 protein amount, was added per well and incubated for the indicated time.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the cellular processing of EGFR, 4 ϫ 10 5 HaCaT cells, plated in 12-well plates, were either left untreated or were IFN-␥ treated (2 ng/ml) overnight. Cells were then incubated with 10 mg/ml cycloheximide for 30 min prior to addition of 100 ng of EGF and incubated for the indicated times.…”

Section: Methodsmentioning

confidence: 99%

Interferon Gamma Prevents Infectious Entry of Human Papillomavirus 16 via an L2-Dependent Mechanism

Day¹,

Thompson²,

Lowy³

et al. 2017

J Virol

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In this study, we report that gamma interferon (IFN-␥) treatment, but not IFN-␣, -␤, or -treatment, dramatically decreased infection of human papillomavirus 16 (HPV16) pseudovirus (PsV). In a survey of 20 additional HPV and animal papillomavirus types, we found that many, but not all, PsV types were also inhibited by IFN-␥. Microscopic and biochemical analyses of HPV16 PsV determined that the antiviral effect was exerted at the level of endosomal processing of the incoming capsid and depended on the JAK2/STAT1 pathway. In contrast to infection in the absence of IFN-␥, where L1 proteolytic products are produced during endosomal capsid processing and L2/DNA complexes segregate from L1 in the late endosome and travel to the nucleus, IFN-␥ treatment led to decreased L1 proteolysis and retention of L2 and the viral genome in the late endosome/lysosome. PsV sensitivity or resistance to IFN-␥ treatment was mapped to the L2 protein, as determined with infectious hybrid PsV, in which the L1 protein was derived from an IFN-␥-sensitive HPV type and the L2 protein from an IFN-␥-insensitive type or vice versa.IMPORTANCE A subset of HPV are the causative agents of many human cancers, most notably cervical cancer. This work describes the inhibition of infection of multiple HPV types, including oncogenic types, by treatment with IFN-␥, an antiviral cytokine that is released from stimulated immune cells. Exposure of cells to IFN-␥ has been shown to trigger the expression of proteins with broad antiviral effector functions, most of which act to prevent viral transcription or translation. Interestingly, in this study, we show that infection is blocked at the early step of virus entry into the host cell by retention of the minor capsid protein, L2, and the viral genome instead of trafficking into the nucleus. Thus, a novel antiviral mechanism for IFN-␥ has been revealed. KEYWORDS HPV, papillomavirus, interferon, IFN-␥, L2P apillomaviruses (PV) are members of a large group of nonenveloped DNA tumor viruses that infect epithelial tissues of a wide range of vertebrate species. A subset of oncogenic mucosal human PV (HPV) types are the causal agents of cervical cancer. These high-risk types, especially HPV16, are also linked to vulvar, vaginal, anal, and oropharyngeal cancers (1). The cascade of viral protein expression is integrally tied to epithelial differentiation, with virion production only occurring in the terminally differentiated upper layers (2). These features combine to allow circumvention of host innate and adaptive immune responses, as few proinflammatory signals are elicited during these early stages (3). However, most PV infections that induce overt hyperproliferation are eventually cleared with the apparent involvement of lymphocytic infiltrates (reviewed in reference 4). Also, HPV infections are often superimposed on colonization with other microbial agents, e.g., in the female reproductive tract (reviewed in reference 5). It is, therefore, of interest to determine if antiviral molecules that are known compon...

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Multiple Infections and Cancer: Implications in Epidemiology

Cited by 45 publications

References 238 publications

Prevalence and genotype distribution of human papillomavirus among Hakka women in China

Prevalence and genotype distribution of human papillomavirus among Hakka women in China

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

Interferon Gamma Prevents Infectious Entry of Human Papillomavirus 16 via an L2-Dependent Mechanism

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